Mycophenolate mofetil as second line immunosuppressant in myasthenia gravis - a long-term prospective open-label study

<p>Abstract</p> <p>Background</p> <p>The preferred immunosuppressive drug for long term treatment of myasthenia gravis (MG) is azathioprine (AZA). Mycophenolate mofetil (MMF) was suggested as an effective and safe second line alternative to AZA.</p> <p>Methods</p> <p>In a prospective open-label study, 11 patients with acetylcholine receptor antibody (AchR-ab) positive MG (n = 4 ocular MG, n = 7 generalized MG) were treated with MMF which replaced AZA. Reasons for the change of immunosuppressant therapy were side effects (n = 9) or unresponsiveness under AZA (n = 3).</p> <p>Results</p> <p>Mean duration of MMF treatment was 16.9 months (6-46 months). During MMF treatment AZA side effects resolved in 8/9 patients, concomitant therapy could be discontinued in 4 patients and reduced in 5 patients, and 5 patients remitted and 3 remained in remission. One MMF-refractory patient required add-on IVIG therapy and another with ocular MG showed signs of generalization after 20 months of MG treatment. One patient was diagnosed with bronchial carcinoma after 10 months of MMF treatment.</p> <p>Conclusion</p> <p>Due to its favourable spectrum of side effects compared to AZA MMF might serve as a second-line immunosuppressant in those MG patients who have not tolerated AZA.</p

A Novel Pathogenic Variant in MT-CO2 Causes an Isolated Mitochondrial Complex IV Deficiency and Late-Onset Cerebellar Ataxia

Both nuclear and mitochondrial DNA defects can cause isolated cytochrome c oxidase (COX; complex IV) deficiency, leading to the development of the mitochondrial disease. We report a 52-year-old female patient who presented with a late-onset, progressive cerebellar ataxia, tremor and axonal neuropathy. No family history of neurological disorder was reported. Although her muscle biopsy demonstrated a significant COX deficiency, there was no clinical and electromyographical evidence of myopathy. Electrophysiological studies identified low frequency sinusoidal postural tremor at 3 Hz, corroborating the clinical finding of cerebellar dysfunction. Complete sequencing of the mitochondrial DNA genome in muscle identified a novel MT-CO2 variant, m.8163A&gt;G predicting p.(Tyr193Cys). We present several lines of evidence, in proving the pathogenicity of this heteroplasmic mitochondrial DNA variant, as the cause of her clinical presentation. Our findings serve as an important reminder that full mitochondrial DNA analysis should be included in the diagnostic pipeline for investigating individuals with spinocerebellar ataxi

Ди-мюонное фоторождение в эксперименте NA64

В работе проанализированы основные процессы, вносящие мюонный вклад в статистику эксперимента NA64. Рассмотрены методы моделирования случайных величин. Разработан Монте-Карло генератор процесса ди-мюонного фоторождения, позволяющий получить энергетические и угловые распределения мюонов.The main processes involved in the muon contribution to the NA64 experiment statistics are analyzed. Methods for modeling random variables are considered. A Monte-Carlo generator was developed for the process of di-muon photoproduction, which makes it possible to obtain energy and angular distributions of muons

A novel pathogenic variant in MT-CO2 causes an isolated mitochondrial complex IV deficiency and late-onset cerebellar ataxia

Both nuclear and mitochondrial DNA defects can cause isolated cytochrome c oxidase (COX; complex IV) deficiency, leading to the development of the mitochondrial disease. We report a 52-year-old female patient who presented with a late-onset, progressive cerebellar ataxia, tremor and axonal neuropathy. No family history of neurological disorder was reported. Although her muscle biopsy demonstrated a significant COX deficiency, there was no clinical and electromyographical evidence of myopathy. Electrophysiological studies identified low frequency sinusoidal postural tremor at 3 Hz, corroborating the clinical finding of cerebellar dysfunction. Complete sequencing of the mitochondrial DNA genome in muscle identified a novel MT-CO2 variant, m.8163A>G predicting p.(Tyr193Cys). We present several lines of evidence, in proving the pathogenicity of this heteroplasmic mitochondrial DNA variant, as the cause of her clinical presentation. Our findings serve as an important reminder that full mitochondrial DNA analysis should be included in the diagnostic pipeline for investigating individuals with spinocerebellar ataxia

A stagewise response to mitochondrial dysfunction in mitochondrial DNA maintenance disorders

\ua9 2024 The AuthorsMitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions arise and accumulate in perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in the accumulation and spread of mtDNA deletions, and that knowledge of how muscle fibres respond to mitochondrial dysfunction is key to our understanding of disease mechanisms. To understand the contribution of mito-nuclear signalling to the spread of mitochondrial dysfunction, we use imaging mass cytometry. We characterise the levels of mitochondrial Oxidative Phosphorylation proteins alongside a mitochondrial mass marker, in a cohort of patients with mtDNA maintenance disorders. Our expanded panel included protein markers of key signalling pathways, allowing us to investigate cellular responses to different combinations of oxidative phosphorylation dysfunction and ragged red fibres. We find combined Complex I and IV deficiency to be most common. Interestingly, in fibres deficient for one or more complexes, the remaining complexes are often upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibres. We further find that oxidative phosphorylation deficient fibres exhibit an increase in the abundance of proteins involved in proteostasis, e.g. HSP60 and LONP1, and regulation of mitochondrial metabolism (including oxidative phosphorylation and proteolysis, e.g. PHB1). Our analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each fibre

Значимые личности в истории города Юрги Кемеровской области

В данной статье впервые даётся авторский взгляд на то, кого из юргинцев можно отнести к наиболее значимым личностям в истории города Юрги Кемеровской области. Предлагается перечень лиц с короткой характеристикой причины их включения. Делается вывод о малоизученности многих вопросов этой темы и её научной перспективности

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS